Group B Streptococcus Vaccine Research Articles

Maternity care provider acceptance of a future Group B Streptococcus vaccine - A qualitative study in three countries.

There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake. This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions. Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine. Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.

Safety and immunogenicity of the group B streptococcus vaccine AlpN in a placebo-controlled double-blind phase 1 trial.

Group B streptococcus (GBS) is a leading cause of life-threatening neonatal infections and subsets of adverse pregnancy outcomes. Essentially all GBS strains possess one allele of the alpha-like protein (Alp) family. A maternal GBS vaccine, consisting of the fused N-terminal domains of the Alps αC and Rib (GBS-NN), was recently demonstrated to be safe and immunogenic in healthy adult women. To enhance antibody responses to all clinically relevant Alps, a second-generation vaccine has been developed (AlpN), also containing the N-terminal domain of Alp1 and the one shared by Alp2 and Alp3. In this study, the safety and immunogenicity of AlpN is assessed in a randomized, double-blind, placebo-controlled, and parallel-group phase I study, involving 60 healthy non-pregnant women. AlpN is well tolerated and elicits similarly robust and persistent antibody responses against all four Alp-N-terminal domains, resulting in enhanced opsonophagocytic killing of all Alp serotypes covered by the vaccine.

Serotype Distribution and Antimicrobial Resistance of Streptococcus agalactiae Isolates in Nonpregnant Adults with Streptococcal Toxic Shock Syndrome in Japan in 2014 to 2021.

The incidence of streptococcal toxic shock syndrome (STSS) due to group B Streptococcus (GBS) has been increasing annually in Japan and is becoming a serious challenge. Furthermore, in recent years, penicillin- or clindamycin-resistant strains used in treating streptococcal toxic shock syndrome have been reported. However, no report analyzed >100 isolates of group B Streptococcus causing streptococcal toxic shock syndrome. Therefore, we aimed to perform serotyping and antimicrobial susceptibility testing of 268 isolated group B Streptococcus strains from streptococcal toxic shock syndrome cases involving nonpregnant adult patients in Japan between 2014 and 2021. The most prevalent serotype was Ib, followed by serotypes V, III, and Ia. Seven isolates were resistant to penicillin G, and 17.9% (48 isolates) were resistant to clindamycin. Of the penicillin-resistant group B Streptococcus isolates, 71.4% (5 isolates) were clindamycin resistant. In addition, group B Streptococcus strains resistant to penicillin and clindamycin were isolated from patients with streptococcal toxic shock syndrome. Therefore, before these strains become prevalent, introduction of the group B Streptococcus vaccine is essential for disease prevention. IMPORTANCE Group B Streptococcus (GBS) has been increasingly associated with invasive disease in nonpregnant adults. Such infections are responsible for substantial morbidity and mortality, particularly in individuals with underlying chronic conditions. Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock, multiorgan failure, and high mortality. In this study, we assessed 268 GBS-related STSS cases in nonpregnant adults in Japan between 2014 and 2021. Serotype Ib was the most prevalent, followed by serotypes V, III, and Ia, which were identified in more than 80% of STSS isolates. We found that 48 clindamycin-resistant strains and 7 penicillin G-resistant strains were isolated between 2014 and 2021. We believe that our study makes a significant contribution to the literature because we show that the GBS vaccine, particularly the hexavalent conjugate vaccine, is important to reduce the number of patients with STSS.

Preparing for Group B Streptococcus vaccine. Attitudes of pregnant women in two countries

ABSTRACT Group B Streptococcus (GBS) vaccines, designed to be given to pregnant women, are in clinical trials. There is an opportunity to conduct preparatory research now to understand the drivers of and barriers to GBS vaccine acceptance. This will enable targeted interventions so that delays in vaccine uptake might be avoided. A multicenter, mixed-methodology, cross-sectional study evaluated the acceptability of a hypothetical GBS vaccine among pregnant women in two countries with differing health systems. Pregnant women in Philadelphia, US, and Dublin, Ireland, completed an electronic survey and a Discrete Choice Experiment. Five hundred and two women were included in the final analysis. Fifty-three percent of US and 30% of Irish participants reported both awareness and understanding of GBS. The median likelihood score for vaccine receipt (measured on a 10-point scale) was 9 (US: 9 (IQR 7–10), IRL: 9 (IQR 6–10)). Among the US participants, identifying as Black or African American was associated with a lower likelihood of vaccine receipt. Possession of a college degree was associated with increased likelihood of vaccine receipt. Perceived infant benefit was the most important driver of GBS vaccine acceptance. Safety concerns about a novel vaccine was the most prominent barrier identified. Good GBS vaccine uptake is achievable through strong messaging that highlights vaccine safety and the potential infant benefits. Preparation for vaccine implementation should include efforts to increase awareness among pregnant women about GBS infection and a continued focus on improving acceptability of currently recommended maternal vaccines, particularly in population subgroups with low uptake of maternal immunizations.

2134. A Phase 2 Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Booster Dose of a Group B Streptococcus 6-Valent Polysaccharide Conjugate Vaccine (GBS6)

Abstract Background Group B streptococcus (GBS) is a leading cause of invasive bacterial infections in young infants and pregnant women. Pfizer is developing a hexavalent GBS vaccine (GBS6) as a maternal vaccine to prevent invasive GBS disease due to the 6 most prevalent serotypes in young infants. We previously reported Phase 1 safety and immunogenicity data for GBS6. There is precedent for repeat doses of vaccines to augment or sustain circulating antibodies available for placental transfer with each pregnancy; thus, data to inform GBS6 booster strategies were required. Methods This was a Phase 2 open-label extension study to evaluate the safety and immunogenicity of a booster dose of GBS6 (20 μg capsular polysaccharide (CPS)/serotype/dose) with or without AlPO4, given ∼2 years after primary vaccination in 151 healthy nonpregnant adults. Sera taken before and 1-month postbooster were assessed for anti-CPS IgG using a direct Luminex immunoassay. Participants recorded solicited local and systemic events for 14 days after vaccination and unsolicited safety events through 6 months after vaccination. Immunogenicity time points from the Phase 1 study are referred to as primary dose. Results Immunogenicity results For all serotypes, serotype-specific IgG geometric mean concentrations (GMCs) remained elevated compared to baseline at the prebooster time point and were higher 1-month postbooster than 1 month post primary. The 1-month postbooster IgG GMCs were 10- to 59-fold higher than at the prebooster time point. There were similar responses between the 2 formulations. Safety and tolerability results The most frequently reported local reaction was mild to moderate pain at the injection site. Greater pain was associated with AlPO4 formulation. The most frequently reported systemic events were mild to moderate headache and fatigue. The frequency of adverse events was low. Figure 1Antibody Response Line Plot of IgG GMCs by Vaccine Group - All SerotypesFigure 2.Reverse Cumulative Distribution Curves (RCDCs) for IgG 1 Month After Primary and Booster Vaccination, by Vaccine Group – All SerotypesFigure 3.IgG Geometric Mean Fold Rises (GMFRs) at 1 Month Postbooster Vaccination Conclusion A booster dose of GBS6 given ∼2 years after a primary dose to healthy nonpregnant adults was safe and elicited robust immune responses that were also consistently higher than after primary dose. This study suggests that repeat vaccination with GBS6 may confer additional benefit in pregnant women in subsequent pregnancies. Disclosures Babalwa Jongihlati, MD, MBA, Pfizer: Stocks/Bonds Judith Absalon, MD, MPH, Pfizer: Stocks/Bonds Samantha Munson, MPH, MBA, Pfizer: Stocks/Bonds Yasmin Sanchez-Pearson, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Natalie Silmon de Monerri, PhD, Pfizer: Stocks/Bonds David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Michelle Gaylord, PhD, Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Stocks/Bonds.

Group B Streptococcus and Pregnancy: Critical Concepts and Management Nuances

Group B Streptococcus (GBS) is a common pathogen with an effective treatment. However, it remains a significant cause of neonatal sepsis, morbidity, and mortality. The screening and management of this infection are some of the first concepts learned during medical training in obstetrics. However, effective screening and evidence-based management of GBS are nuanced with many critical caveats. The objectives of this review are to discuss the essential aspects of GBS screening and management and to highlight recent changes to recommendations and guidelines. Original research articles, review articles, and guidelines on GBS were reviewed. The following recommendations are based on review of the evidence and professional society guidelines. Screening for GBS should occur between 36 weeks and the end of the 37th week. The culture swab should go 2 cm into the vagina and 1 cm into the anus. Patients can perform their own swabs as well. Penicillin allergy testing has been shown to be safe in pregnancy. Patients with GBS in the urine should be treated at term with antibiotic prophylaxis, independent of the colony count of the culture. Patients who are GBS-positive with preterm and prelabor rupture of membranes after 34 weeks are not candidates for expectant management, as this population has higher rates of neonatal infectious complications. Patients with a history of GBS colonization in prior pregnancy who are GBS-unknown in this current pregnancy and present with labor should receive intrapartum prophylaxis. Work on the GBS vaccine continues. Although all of the efforts and focus on neonatal early-onset GBS infection have led to lower rates of disease, GBS still remains a major cause of neonatal morbidity and mortality requiring continued vigilance from obstetric providers.

Attenuated Streptococcus agalactiae WC1535 ∆Sia perturbs the gut microbiota of Oreochromis niloticus, massively colonizes the intestine, and induces intestinal mucosal immunity after intraperitoneal inoculation.

We previously developed and assessed the effectiveness of the attenuated Streptococcus agalactiae (Group B Streptococcus, GBS) strain WC1535 ∆Sia (with neuA-D gene cluster deletion) vaccine in tilapia (Oreochromis niloticus). In this study, we characterized the bacterial communities of the tilapia intestines by 16S rRNA high-throughput sequencing and assessed the serum antibody response, expression of immune-related genes, and histological changes following formalin-killed GBS vaccine (FKV) and the live attenuated vaccine ∆Sia (LAV). Results showed that FKV and LAV induced robust systemic and intestinal mucosal immune responses in tilapia without causing obvious pathological changes in the hindgut, spleen, and head kidney but exerted different effects on intestinal bacterial communities. The richness or diversity of the intestinal bacterial community of FKV tilapia showed no significant changes compared with that of the control fish (p > 0.05) at either day 21 post-initial vaccination (21 dpiv) or day 35 (day 14 after the second immunization) (35 dpiv). The community composition of FKV tilapia and controls was significantly similar, although the relative abundance of some genera was significantly altered. Relative to control fish, the gut ecosystem of LAV tilapia was significantly disturbed with a substantial increase in community diversity at 21 dpiv (p < 0.05) and a significant decrease at 35 dpiv in fish with high serum antibody response (ΔSia35H) (p < 0.05). However, there was no significant difference between ΔSia35H and ΔSia35L (low serum antibody response) fish (p > 0.05). Moreover, the community composition of LAV tilapia at 21 dpiv or 35 dpiv was considerably different from that of the controls. Particularly, GBS ∆Sia was found to be abundant in the intestine at 21 and 35 dpiv. This result suggested that the parenteral administration of the LAV (∆Sia) may also have the effect of oral vaccination in addition to the immune effect of injection vaccination. In addition, a significant correlation was found between the expression of immune-related genes and certain bacterial species in the intestinal mucosal flora. Our findings will contribute to a better understanding of the effects of inactivated and attenuated vaccines on gut microbiota and their relationship with the immune response.

Rectovaginal Colonization with Serotypes of Group B Streptococci with Reduced Penicillin Susceptibility among Pregnant Women in León, Nicaragua.

Group B Streptococci (GBS) are important causes of neonatal sepsis and meningitis globally. To elucidate the potential benefits of maternal GBS vaccines, data is needed on the epidemiology of maternal GBS rectovaginal colonization, distribution of serotypes, and resistance to intrapartum antibiotic prophylaxis (IAP). We collected rectal and vaginal samples from 305 pregnant women in León, Nicaragua between 35 and 40 weeks gestation. Samples were cultured for GBS and confirmed using latex agglutination. GBS isolates underwent serotyping by quantitative polymerase chain reaction, and antimicrobial susceptibility testing by disk diffusion and microdilution following Clinical Laboratory Standard Institute guidelines. Sixty-three women (20.7%) were colonized with GBS in either the rectum or the vagina. Of 91 GBS isolates collected from positive cultures, most were serotypes II (28.6%), Ia (27.5%), and III (20.9%). Most GBS isolates (52.9%) were resistant to penicillin, the first-line prophylactic antibiotic. Penicillin resistance was highly correlated with resistance to vancomycin, ceftriaxone, and meropenem. The results of our study suggest that one-fifth of pregnant women in the urban area of León, Nicaragua are colonized with GBS and risk transmitting GBS to their offspring during labor. High resistance to commonly available antibiotics in the region suggests that prophylactic maternal GBS vaccination would be an effective alternative to IAP.

Clinical Risk Factors Associated With Late-Onset Invasive Group B Streptococcal Disease: Systematic Review and Meta-Analyses.

BackgroundGroup B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood.MethodsWe conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk.ResultsWe included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43–7.22), low birth weight (OR 6.73; 95% CI: 4.68–9.67), maternal colonization (2.67; [2.07–3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19–12.38) were associated with an increased risk of LOGBS.ConclusionsPrematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants.

Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the UK between 2014 and 2015.

Cases of invasive group B streptococcal infection in the adult UK population have steadily increased over recent years, with the most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of the whole-genome sequences of 193 clinically important group B Streptococcus (GBS) isolates (184 were from invasive infection, 8 were from non-invasive infection and 1 had no information on isolation site) isolated from adults and submitted to the National Reference Laboratory at the UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.9%), Ia (26.4%) and V (15.0%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=182) grouped to five clonal complexes (CCs), CC1, CC8/CC10, CC17, CC19 and CC23, with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between sequence type (ST)1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); between ST19 serotype III and serotype V (n=5 isolates); and between CC17 serotype III and serotype IV (n=1 isolate). The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand the global spread of GBS serotypes and genotypes, and will form the baseline information for any future GBS vaccine research in the UK and worldwide.

Epidemiology and bacterial characteristics of invasive group B streptococcus disease: a population-based study in Japan in 2010-2020.

This is the first report on a population-based prospective study of invasive group B streptococcus (GBS) disease among children aged <15 years conducted over a period of 11 years in Japan. This study investigated the incidence and clinical manifestations of invasive GBS disease in children in Chiba Prefecture, Japan, and analysed the serotypes and drug susceptibility of GBS strains isolated during the study period. Overall, 127 episodes of invasive GBS disease were reported in 123 patients. Of these, 124 were observed in 120 patients aged <1 year, and the remaining three episodes were reported in a 9-year-old child and two 14-year-old children with underlying disease. For patients aged <1 year, the incidence rate per 1000 live births was 0.24 (0.15-0.36). The incidences of early-onset disease and late-onset disease were 0.04 (0.0-0.09) and 0.17 (0.08-0.25), respectively. The rate of meningitis was 45.2%, and the incidence of GBS meningitis was higher than that of other invasive diseases among children in Japan. Of the 109 patients for whom prognosis was available, 7 (6.4%) died and 21 (19.3%) had sequelae. In total, 68 strains were analysed. The most common were serotype III strains (n = 42, 61.8%), especially serotype III/ST17 strains (n = 22, 32.4%). This study showed that the incidence of invasive GBS disease among Japanese children was constant during the study period. Because of the high incidence of meningitis and disease burden, new preventive strategies, such as GBS vaccine, are essential.

A REVIEW OF GROUP B STREPTOCOCCUS (GBS) VAGINAL COLONIZATION AND ASCENDING INTRAUTERINE INFECTION: INTERACTION BETWEEN HOST IMMUNE RESPONSES AND GBS VIRULENCE FACTORS

Vaginal colonization with Group B streptococcus (GBS) or Streptococcus agalactiae can potentially cause ascending intrauterine infection among pregnant women, and hence it is known as one of the risk factors for preterm delivery. Ascending intrauterine infection may also cause the transmission of GBS to the fetus in utero and the newborn during delivery, leading to the development of early onset of neonatal infection. GBS are β-hemolytic, gram-positive bacteria that are opportunistic commensal of the gastrointestinal and urogenital tract of approximately 18% of pregnant women globally. Intrapartum antibiotic prophylaxis (IAP) only reduces the rate of early onset neonatal infection, but not the late onset neonatal infection. Thus, the development of GBS vaccine is thought to be important to decrease the rate of preterm delivery and neonatal infections particularly in low-and-middle income countries where IAP program is not feasible. Vaccination can also be cost-effective for the healthcare system when executed together with IAP program. The aim of the current review is to summarize the mechanisms on how the GBS virulence factors interact with host immune components in the gestational tissues, leading to cervicovaginal colonization and ascending intrauterine infection. The elucidation of these mechanisms is essential for expediting the development of vaccines and novel therapeutic measures targeting these GBS virulence factors that will hamper the vaginal colonization, ascending intrauterine infection and conceptus tissue invasion by GBS. These strategies are crucial to potentially reduce the rate of preterm delivery and subsequent serious complications in the newborn.

Serotyping of invasive and colonizing group B Streptococcus (GBS) isolates at selected hospitals in Sri Lanka: a multicenter study.

Group B Streptococcus (GBS) causes significant morbidity and mortality in neonates, pregnant women and patients with underlying comorbidities. Intrapartum antibiotic prophylaxis (IAP) is currently the mainstay of prevention and effective vaccine against invasive GBS disease is under clinical trial. To describe the serotype distribution of invasive and colonizing GBS isolates in Sri Lanka. Probable GBS isolates from high vaginal swabs (HVS) and sterile body sites were collected from eight selected hospital laboratories. Following confirmation of the identification as group B Streptococcus by phenotypic methods including Lancefield grouping test (Plasmatic UK), isolates were tested for serotyping by latex agglutination test kit (STATEN serum institute, Denmark). Out of the 145 probable GBS isolates only 100 from HVS and 37 from sterile body sites were confirmed as GBS. Serotype III was the most predominant in invasive GBS isolates followed by Ia, Ib, VI, II and V in the descending order of frequency. Serotype VI was the most predominant in HVS isolates followed by serotype III, V, Ia, II, Ib and IV. Difference of GBS serotype distribution between the invasive and HVS group was statistically significant (P value = 0.038). Serotype distribution pattern of the study isolates was comparable to most of the other developing and developed countries and hence will be beneficial in future vaccine introduction. GBS vaccine which is currently under clinical trial (Ia, Ib and III) is potentially effective for preventing 68% of the early onset disease in neonates in this study setting.

Invasive Group B Streptococcal Disease in Neonates and Infants, Italy, Years 2015-2019.

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015–2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine.

High rates of colonization and antimicrobial resistance of group B streptococcus highlight the need for vaccination even after implementation of guidelines for intrapartum antibiotic prophylaxis

IntroductionIt is estimated that about 11–35% of pregnant women are colonized with Group B streptococcus. Intrapartum antibiotic prophylaxis (IAP) is the primary intervention to decrease the risk of infecting babies born to GBS colonized mothers. MethodsA total of 5,996 pregnant women, who received the Taiwanese universal GBS screening program from 2012 to 2020, were included in this study that investigated GBS colonization, antimicrobial resistance rates and their neonatal incidence of invasive GBS infection. ResultsThe average GBS colonization rate was 18.5%. Older age groups had higher colonization rates than younger age groups. Compared to Taiwanese, immigrant women from Indonesia had a greater positive rate. GBS isolated from Vietnamese women had significant greater resistance to clindamycin relative to Taiwanese women. Rates of resistance to erythromycin increase from 35.5% to 45.5% over the 9 years of measurements. The incidence of invasive GBS disease was about 0.6/1,000 (4/6,204) live births during the study. ConclusionsAlthough relatively low incidence of invasive GBS diseases was observed after implementation of IAP, the colonization of GBS remains high and antimicrobial resistance of GBS is increasing. An effective GBS vaccine holds promise to be a solution for these issues.

Serotype distribution and incidence of invasive early onset and late onset group B streptococcal disease amongst infants in Singapore

BackgroundThe current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD.MethodsA retrospective study of infants ≤ 90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared.ResultsA total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD.ConclusionsThe LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.

Stakeholder Perceptions About Group B Streptococcus Disease and Potential for Maternal Vaccination in Low- and Middle-Income Countries.

BackgroundTo inform the World Health Organization’s full value of vaccine assessment for group B Streptococcus (GBS) vaccines, a rapid literature appraisal was conducted to inform the operationalization of maternal GBS vaccination. We found limited published information on stakeholder perceptions of the public health importance of GBS disease and vaccination, and we therefore undertook a multicountry survey.MethodsAn online survey was conducted in late 2019 to collect information on stakeholders’ awareness of GBS disease and the priority accorded to vaccination. The survey was distributed by email to 395 representatives of national pediatric, gynecology, and obstetrics associations, national immunization technical advisory groups (NITAGs), national regulatory agencies, academia, and United Nations organizations.ResultsAmong 101 survey respondents from 66 countries, 36% were pediatricians, 25% obstetricians/gynecologists, 21% immunization specialists, and 18% other public health specialists. More than half (58%) of respondents reported being familiar with GBS disease as a public health problem; familiarity decreased by country income level. Knowledge of GBS disease was greatest in the Americas (68%) and Europe (66%) and lowest in Asia (13%–38%). Perception of GBS disease as a public health problem was highest among pediatricians (71%) and lowest among public health policy makers and NITAG members (30%) across country groupings. Approximately half of respondents (49%) considered the introduction of a GBS vaccine as a priority.ConclusionsThe information obtained will inform the appropriate packaging and presentation of information to address stakeholder perceptions and promote evidence-based decision making on GBS vaccination.

A Financial and Global Demand Analysis to Inform Decisions for Funding and Clinical Development of Group B Streptococcus Vaccines for Pregnant Women.

BackgroundDespite group B Streptococcus (GBS) being a leading cause of maternal and infant morbidity and mortality, no vaccine is currently available. To inform vaccine developers, countries, and funders, we analyzed the key factors likely to influence the demand for a GBS vaccine and the long-term financial sustainability for a vaccine developer.MethodsUsing population-based forecasting, we estimated the demand for a GBS vaccine; using a discounted cash flow model we estimated the financial viability for a vaccine developer.ResultsDemand for this vaccine can be significant if countries adopt policy recommendations for use, in particular, the largest ones, most of which have a burden that justifies use of the vaccine, and if financing for the vaccine is made available either by countries or by funding mechanisms such as Gavi, the Vaccine Alliance.ConclusionsThis analysis suggests the potential for financial and commercial viability for a vaccine developer pursuing the commercialization of a GBS vaccine. Risks exists in relation to the clinical trial design and costs, the level of competition, countries’ ability to pay, the administration schedule, and the availability of policies that encourage use of the vaccine. To reduce those risks and ensure equitable access to a GBS vaccine, the role of donors or financers can prove very important, as can a coordinated operational research agenda that aims at clarifying those areas of uncertainty.

Group B streptococcal infections in infants in Iceland: clinical and microbiological factors.

IntroductionGroup B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7–89 days), with different GBS clonal complexes (CCs) associated with different disease presentations.Hypothesis/Gap StatementDifferent GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia).AimTo study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland?MethodologyAll culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records.ResultsA total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001).ConclusionCC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.

Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy.

Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.